We are more than 20 years into the HIV/AIDS epidemic. Although much is known about event-specific behaviors and contexts that facilitate HIV and HCV transmission among injecting drug users (IDUs), we know very little about the mechanisms by which many long-time IDUs have managed to remain uninfected with either virus. Given the psychological, behavioral and social problems and chaotic lives that drug injectors often face, and the ways in which these may predispose them to engage in risky behaviors in high-risk settings, it is a puzzle how some nonetheless remain uninfected over the long term. We aim to discover strategies, resources, practices, and prevention tactics that help IDUs to remain uninfected, as well as the obstacles they face and the ways in which they overcome these obstacles. We will do this by conducting detailed life history interviews with 80 long-term current IDUs who fall into two distinct categories by infection status: (1) Doubly uninfected who are both HIV- and HCV-antibody negative; and (2) Doubly infected who are positive for both viruses. Qualitative analyses will compare and contrast the life histories of IDUs in these categories to discover how they differ in terms of strategies, socioeconomic resources, use of drug treatment and other services, and approaches to risk and risk-avoidance. Person-centered quantitative analysis methods will be used to discover additional differences between the life pathways of the two groups. We will also develop and assess a questionnaire module to measure concepts that emerge as important. This will facilitate 3 new areas of related research: 1. Epidemiologic verification; 2. Development and evaluation of prevention programs based on project findings; and 3. Etiologic research to determine physiological, psychological and social causal factors that make some IDUs more likely to implement strategies that offer a degree of long term protection from infection. This project will provide the conceptual basis for developing a new generation of HIV and HCV prevention programs to assist IDUs who are unable to quit injecting to develop strategies to avoid infection over the long run and to make better use of existing forms of prevention and treatment.